96 : Evolutionary conservation of STING, an innate immune effector and DNA sensor, in Drosophila melanogaster

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The innate immune response provides the first line of defense against pathogens by responding to foreign molecules, such as cytosolic DNA or double-stranded RNA, by-products of bacterial and viral infections. The mammalian protein STING (STimulator of INterferon Genes), an intracellular sensor to by-products of pathogenic infection, is critical to the innate immune response and the induction of interferon beta, a potent antimicrobial molecule. In Drosophila, fat body cells contain surface receptors for the detection of pathogens in the hemolymph. Activation of these receptors stimulates the innate immune response, which is potentiated by the induction of antimicrobial peptides. While the mechanisms of cell surface receptor signaling in Drosophila are well understood, less is known about the intracellular sensors to pathogenic infection. Here we describe the identification of a Drosophila homologue of human STING, dSTING. We show that dSTING is a transmembrane protein that localizes to the endoplasmic reticulum. dSTING is capable of binding nucleic acids, which results in its perinuclear translocation, presumably necessary for the induction of antimicrobial peptides. In both S2 cells and adult flies, the loss of dSTING by RNA interference results in increased pathogen replication and mortality, correlated to decreased antimicrobial induction. Functional genomics analysis shows that the loss of dSTING results in the inability of flies to mount an innate immune response upon pathogenic infection. These results suggest that dSTING is the evolutionary ancestor of cytosolic pathogen-associated nucleic acid-sensing, responsible for a proper immune response to infection.